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Q9WTX4

- NRG4_MOUSE

UniProt

Q9WTX4 - NRG4_MOUSE

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Protein

Pro-neuregulin-4, membrane-bound isoform

Gene

Nrg4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors.1 Publication

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiREACT_188191. Signaling by ERBB2.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188579. Signaling by ERBB4.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198574. Nuclear signaling by ERBB4.
REACT_203296. PI3K events in ERBB4 signaling.
REACT_215348. PI3K events in ERBB2 signaling.
REACT_226341. PIP3 activates AKT signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-neuregulin-4, membrane-bound isoform
Short name:
Pro-NRG4
Cleaved into the following chain:
Neuregulin-4
Short name:
NRG-4
Gene namesi
Name:Nrg4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1933833. Nrg4.

Subcellular locationi

Chain Pro-neuregulin-4, membrane-bound isoform : Cell membrane By similarity; Single-pass type I membrane protein By similarity
Note: Does not seem to be active.By similarity

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 115115Pro-neuregulin-4, membrane-bound isoformPRO_0000019487Add
BLAST
Chaini1 – 6161Neuregulin-4PRO_0000019488Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi9 ↔ 23PROSITE-ProRule annotation
Disulfide bondi17 ↔ 34PROSITE-ProRule annotation
Disulfide bondi36 ↔ 45PROSITE-ProRule annotation
Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi60 – 601N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.By similarity
Extensive glycosylation precedes the proteolytic cleavage.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ9WTX4.

Expressioni

Tissue specificityi

Highly expressed in pancreas; weakly expressed in muscle.

Gene expression databases

BgeeiQ9WTX4.
CleanExiMM_NRG4.
ExpressionAtlasiQ9WTX4. baseline and differential.
GenevestigatoriQ9WTX4.

Interactioni

Subunit structurei

Interacts with ERBB4.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000079037.

Structurei

3D structure databases

ProteinModelPortaliQ9WTX4.
SMRiQ9WTX4. Positions 14-48.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6262ExtracellularSequence AnalysisAdd
BLAST
Topological domaini84 – 11532CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei63 – 8321Helical; Note=Internal signal sequenceSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 4642EGF-likePROSITE-ProRule annotationAdd
BLAST

Domaini

The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).By similarity
ERBB receptor binding is elicited entirely by the EGF-like domain.By similarity

Sequence similaritiesi

Belongs to the neuregulin family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42904.
GeneTreeiENSGT00390000014815.
HOGENOMiHOG000113853.
HOVERGENiHBG006533.
InParanoidiQ9WTX4.
KOiK05458.
OMAiNGGICYM.
PhylomeDBiQ9WTX4.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view]
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 1 isoform i produced by alternative splicing. Align

Note: At least 3 isoforms may be produced.

Isoform 1 (identifier: Q9WTX4-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPTDHEQPCG PRHRSFCLNG GICYVIPTIP SPFCRCIENY TGARCEEVFL
60 70 80 90 100
PSSSIPSESN LSAAFVVLAV LLTLTIAALC FLCRKGHLQR ASSVQCEISL
110
VETNNTRTRH SHREH
Length:115
Mass (Da):12,744
Last modified:November 1, 1999 - v1
Checksum:i989A1E376F857B49
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF083067 mRNA. Translation: AAD21874.1.
CCDSiCCDS52801.1. [Q9WTX4-1]
RefSeqiNP_114391.1. NM_032002.2. [Q9WTX4-1]
XP_006511631.1. XM_006511568.1. [Q9WTX4-1]
XP_006511632.1. XM_006511569.1. [Q9WTX4-1]
XP_006511633.1. XM_006511570.1. [Q9WTX4-1]
UniGeneiMm.443874.

Genome annotation databases

EnsembliENSMUST00000130158; ENSMUSP00000115247; ENSMUSG00000032311. [Q9WTX4-1]
ENSMUST00000164721; ENSMUSP00000130929; ENSMUSG00000032311. [Q9WTX4-1]
GeneIDi83961.
KEGGimmu:83961.
UCSCiuc009psf.2. mouse. [Q9WTX4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF083067 mRNA. Translation: AAD21874.1 .
CCDSi CCDS52801.1. [Q9WTX4-1 ]
RefSeqi NP_114391.1. NM_032002.2. [Q9WTX4-1 ]
XP_006511631.1. XM_006511568.1. [Q9WTX4-1 ]
XP_006511632.1. XM_006511569.1. [Q9WTX4-1 ]
XP_006511633.1. XM_006511570.1. [Q9WTX4-1 ]
UniGenei Mm.443874.

3D structure databases

ProteinModelPortali Q9WTX4.
SMRi Q9WTX4. Positions 14-48.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000079037.

Proteomic databases

PRIDEi Q9WTX4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000130158 ; ENSMUSP00000115247 ; ENSMUSG00000032311 . [Q9WTX4-1 ]
ENSMUST00000164721 ; ENSMUSP00000130929 ; ENSMUSG00000032311 . [Q9WTX4-1 ]
GeneIDi 83961.
KEGGi mmu:83961.
UCSCi uc009psf.2. mouse. [Q9WTX4-1 ]

Organism-specific databases

CTDi 145957.
MGIi MGI:1933833. Nrg4.

Phylogenomic databases

eggNOGi NOG42904.
GeneTreei ENSGT00390000014815.
HOGENOMi HOG000113853.
HOVERGENi HBG006533.
InParanoidi Q9WTX4.
KOi K05458.
OMAi NGGICYM.
PhylomeDBi Q9WTX4.

Enzyme and pathway databases

Reactomei REACT_188191. Signaling by ERBB2.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188579. Signaling by ERBB4.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198574. Nuclear signaling by ERBB4.
REACT_203296. PI3K events in ERBB4 signaling.
REACT_215348. PI3K events in ERBB2 signaling.
REACT_226341. PIP3 activates AKT signaling.

Miscellaneous databases

NextBioi 350830.
PROi Q9WTX4.
SOURCEi Search...

Gene expression databases

Bgeei Q9WTX4.
CleanExi MM_NRG4.
ExpressionAtlasi Q9WTX4. baseline and differential.
Genevestigatori Q9WTX4.

Family and domain databases

InterProi IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view ]
SMARTi SM00181. EGF. 1 hit.
[Graphical view ]
PROSITEi PS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase."
    Harari D., Tzahar E., Romano J., Shelly M., Pierce J.H., Andrews G.C., Yarden Y.
    Oncogene 18:2681-2689(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ERBB4.
    Strain: C57BL/6J.
    Tissue: Liver.

Entry informationi

Entry nameiNRG4_MOUSE
AccessioniPrimary (citable) accession number: Q9WTX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: October 29, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3